The principal investigator is a Research Assistant Professor in Northwestern University's Center for Sleep and Circadian Biology. She seeks training in the molecular genetics of circadian rhythms to complement her current skills. Her long-term goal is to study circadian rhythms and their development. Circadian rhythms are predictable daily changes in behavior and physiology. Driven by an internal biological clock, they have profound clinical relevance to diagnosis and treatment of disease and to sleep and affective disorders. The core of all known circadian clocks is a cell-autonomous transcriptional feedback loop, well-conserved between Drosophila and mice. In both species a central component is the Clock (Clk) gene. In flies its ectopic expression induces ectopic circadian clocks. The immediate research goal of this proposal is to determine the role of the Clock gene in organizing these molecular oscillations, a defining step in clock development. Specifically, genetic requirements for clock induction in Drosophila will be tested with ectopic CIk expression in mutants for genes that regulate or partner with CLK, and by misexpression of these other clock genes. A developmental requirement for CIk in organizing endogenous clocks will be examined by conditional rescue of Clk at various developmental times using molecular genetic approaches. The generality of these results will be tested by determining if transgenic expression of the mouse Clock gene is able to induce ectopic clocks in mice. The studies will be conducted at Northwestern University under the mentorship of and in collaboration with an internationally renowned mammalian geneticist (J. Takahashi) and a rising young fly geneticist (R. Allada). Here, the Center for Sleep and Circadian Biology provides a stimulating and dynamic environment for training in biological rhythms. In conjunction with a didactic program and individual mentoring, the [candidate] will gain training and experience in the molecular genetics of circadian rhythms in fly and mouse models. These techniques will complement her anatomical skills. In addition, training in the field of circadian rhythms will allow synthesis of many aspects of her previous work which include vertebrate and invertebrate studies on the ontogeny of networks underlying behavior. It is expected that this will allow her to develop into a mature circadian researcher studying the development of the biological clock.